The program of the Unit on Neuronal Secretory Systems is focused on studying the biochemistry and physiology of the nerve terminal using the neurohypophysial neuroendocrine cells as the model system. These include studies on the properties of the neurosecretory vesicle membranes which take part in the exocytotic secretory process at the terminal, and has led to the development and consolidation of the secretory vesicle hypothesis in the Laboratory of Neurochemistry and Neuroimmunology. The neurosecretory vesicles were shown to have an intravesicular pH of 5.5 brought about by an electrogenic H+ translocating Mg++ -ATPase on the membrane. The cytochrome b561, also present on the vesicle membrane together with the intravesicular ascorbic acid, functions to transport electrons across the membrane and thus support a peptide amidating enzyme within the neurosecretory vesicles. Recently, a preparation of highly purified nerve endings (neurosecretosomes) has been obtained in order to study the kinetics of neuropeptide secretion from these terminals in vitro. Fractionation of membranes prepared from these neurosecretosomes led to th identification of non-mitochondrial Ca++ -sequestering membrane system inside the nerve terminals. Optical methods have been used to record action potentials in intact neurohypophysial nerve terminals, and have also revealed light scattering signals correlated with secretion.